In the mature nervous system most nerve cells are post-mitotic, and this cannot be replaced. The long-term goal is to elucidate the factors maintaining functional viability in the mature nervous system. In adults, increased age diminishes the viability of certain neurons and not of others. This differential effect of age on viability may be pathway dependent: A pathway mediating sensory-initiated behavior appears more age-sensitive than a pathway mediating CNS-initiated behavior. The animal model developed in this laboratory to investigate neuronal viability is the Aplysia, a marine mollusc. It is ideal; because, the same neurons are identifiable in different aged animals and are of known function; and differential sensitivity to age occurs among these neurons. The objective of this proposal is to examine by cellular techniques the trophic effect of afferent activity on long-term functional viability of neurons. 1) To determine if sensory activity changes with increased age, it will be investigated in two pathways whose dependence on the activity is different and respond differently to age. i) The gill withdrawal reflex is sensory-initiated; it and its substrates are age-sensitive. ii) Gill respiratory pumping is CNS-initiated; it and its substrates are age-invariant. 2) Trophic influence of sensory activity on neuron function in the two pathways will be tested by a) chronic stimulation of sensory input and by b) chronic absence of sensory input. Aplysia neurons and those in the mammalian nervous system share many of the same properties, that includes reduced viability with increased age. This age-sensitivity then is conserved across species. Studies proposed here will help characterize factors mediating neuron viability, and the findings are extrapolatable to higher vertebrates. Trophic factors are probably involved in its long-term viability as well as in development of the nervous system, hence it is questionable if neuron deterioration and death are the only consequences of increased age.